Suppression of apoptosis by overexpression of Bcl-2 or Bcl-xL promotes survival and mutagenesis after oxidative damage.
Apoptosis is the physiological process by which unwanted cells in an organism are killed. Bcl-2, a membrane-bound cytoplasmic protein, and its close relative Bcl-xL, are both effective inhibitors of apoptosis induced by a wide variety of stimuli in many different cell types. In a previous study, we reported that suppression of apoptosis by Bcl-2 or Bcl-xL, markedly elevates the levels of radiation-induced mutations at the specific locus thymidine kinase. We investigated the effect of the Bcl-2 or Bcl-xL overproduction on hydrogen peroxide-induced mutagenesis. Oxidative DNA damage has been implicated in biological processes such as mutagenesis, carcinogenesis and aging. Overexpression of either Bcl-2 or Bcl-xL enhances oxidative stress mutagenesis in cells with wild type p53 as well as with mutated p53 protein. These results support the hypothesis that apoptosis plays a crucial role in maintaining genomic integrity by selectively eliminating highly mutated cells from the population.
Cherbonnel-Lasserre
C
C
Life Sciences Division, Lawrence Berkeley Laboratory, University of California 94720, USA.
Dosanjh
M K
MK
D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D016296:Mutagenesis / Q000187:drug effects; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D006861:Hydrogen Peroxide; C022616:thiazolyl blue